Neurochemical Research

, Volume 38, Issue 3, pp 504–511 | Cite as

Comparison and Effects of Acute Lamotrigine Treatment on Extracellular Excitatory Amino Acids in the Hippocampus of PTZ-Kindled Epileptic and PTZ-Induced Status Epilepticus Rats

  • Yan Deng
  • Minghuan Wang
  • Wei Wang
  • Chao Ma
  • Nongyue He
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

In this communication, the effect of acute treatment with lamotrigine (LTG) was investigated on release of main excitatory amino acids (EAA) such as glutamate (Glu) and aspartate (Asp) in the hippocampus of pentylenetetrazol (PTZ)-induced and PTZ-kindled freely moving rats using micro dialysis. The results show that, levels of Glu and Asp significantly increased in the rat hippocampus during the seizure/interical periods for PTZ-status epilepticus (SE) and PTZ-kindled epileptic (EP) rats. The levels of Glu and Asp increased more in EP rat hippocampus than in SE rat hippocampus. After administration of 20 mg/kg LTG, the levels of Glu and Asp significantly decreased in the SE and EP rat hippocampus. The results indicate that: (a) excitability of the PTZ-kindled epileptogenic model is higher than that of the status epilepticus model; (b) the modulation of LTG on the EAA neurotransmitters certainly plays an important role in antiepileptic efficacy, especially in PTZ-kindled epileptic model where the release of EAA was influenced more markedly by acute application of 20 mg/kg LTG.

Keywords

Lamotrigine (LTG) Pentylenetetrazol (PTZ) Epilepsy Excitatory amino acid (EAA) Effect Comparison 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This work was financially supported by the Chinese 973 Project (No. 2010CB933903), the Natural Science Foundation of China (NO. 60971045), Hunan Science and Technology Projects (NO. 2012SK3105), the Natural Science Foundation of Hunan Province, China (NO. 12JJ6060), the Research Foundation of Education Bureau of Hunan Province, China (NO. 11A030).

References

  1. 1.
    Bazil CW (2002) New antiepileptic drugs. Neurol 8:71–81CrossRefGoogle Scholar
  2. 2.
    Kwan P, Sills GJ, Brodie MJ (2001) The mechanism of action of commonly used antiepileptic drugs. Pharmacol Ther 90:21–34PubMedCrossRefGoogle Scholar
  3. 3.
    Ferrie CD, Panayiotopoulos CP (1994) Therapeutic interaction of lamotrigine and sodium valproate in intractable myoclonic epilepsy. Seizure 3:157–159PubMedCrossRefGoogle Scholar
  4. 4.
    Ferrie CD, Robinson RO, Knott C, Panayiotopoulos CP (1995) Lamotrigine as an add-on drug in typical absence seizures. Acta Neurol Scand 91:200–202PubMedCrossRefGoogle Scholar
  5. 5.
    Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A (1999) The efficacy of valproate lamotrigine comedication in refactory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia 40:1141–1146PubMedCrossRefGoogle Scholar
  6. 6.
    Hwang H, Kim H, Kim SH, Kim SH, Lim BC, Chae JH, Choi JE, Kim KJ, Hwang YS (2012) Long-term effectiveness of ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. Brain Dev 34:344–348PubMedCrossRefGoogle Scholar
  7. 7.
    Arban R, Maraia G, Brackenborough K, Winyard L, Wilson A, Gerrard P, Large C (2005) Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania. Behav Brain Res 158:123–132PubMedCrossRefGoogle Scholar
  8. 8.
    Coderre TJ, Kumar N, Lefebvre CD, Yu JSC (2007) A comparison of the glutamate release inhibition and anti-allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain. J Neurochem 100:1289–1299PubMedCrossRefGoogle Scholar
  9. 9.
    Lee HJ, Ertley RN, Rapoport SI, Bazinet RP, Rao JS (2008) Chronic administration of lamotrigine downregulates COX-2 mRNA and protein in rat frontal cortex. Neurochem Res 33:861–866PubMedCrossRefGoogle Scholar
  10. 10.
    Chang YYC, Rapoport SI, Rao JS (2009) Chronic administration of mood stabilizers upregulates BDNF and Bcl-2 expression levels in rat frontal cortex. Neurochem Res 34:536–541PubMedCrossRefGoogle Scholar
  11. 11.
    Cunningham MO, Jones RSG (2000) The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vivo. Neuropharmacol 39:2139–2141CrossRefGoogle Scholar
  12. 12.
    Cunninham MO, Dhillon A, Wood SJ, Jones RS (2000) Reciprocal modulation of glutamate and GABA release may underlie the anticonvulsant effect of phenytoin. Neurosci 95:343–351CrossRefGoogle Scholar
  13. 13.
    Shuaib A, Mahmood RH, Wishart T, Kanthan R, Murabit MA, Ijas S, Miyashita H, Howlett W (1995) Neuroprotective effects of lamotrigine in global ischaemia in gerbils. A histological in vivo microdialysis and behavioural study. Brain Res 702:199–206PubMedCrossRefGoogle Scholar
  14. 14.
    Bacher A, Zornow MH (1997) Lamotrigine inhibits extracellular glutamate accumulation during transient global ischaemia in rabbits. Anaesthesiol 86:459–463CrossRefGoogle Scholar
  15. 15.
    Ahmad S, Fowler LJ, Whitton PS (2004) Effects of acute and chronic lamotrigine treatment on basal and stimulated extracellular amino acids in the hippocampus of freely moving rats. Brain Res 1029:41–47PubMedCrossRefGoogle Scholar
  16. 16.
    Paraskevas GP, Triantafyllou NI, Kapaki E, Limpitaki G, Petropoulou O, Vassilopoulos D (2006) Add-on lamotrigine treatment and plasma glutamate levels in epilepsy: relation to treatment response. Epilepsy Res 70:184–189PubMedCrossRefGoogle Scholar
  17. 17.
    Eriksson A-S, O’Connor WT (1999) Analysis of CSF amino acids in young patients with generalized refractory epilepsy during an add-on study with lamotrigine. Epilepsy Res 34:75–83PubMedCrossRefGoogle Scholar
  18. 18.
    Tomczyk T, Haberek G, Zuchora B, Jaroslawska-Zych A, Kowalczyk MS, Wielosz M, Urbanska EM (2007) Enhanced glutamatergic transmission reduces the anticonvulsant potential of lamotrigine but not of felbamate against tonic-clonic seizures. Pharmacological Repor 59:462–466Google Scholar
  19. 19.
    Lee C-Y, Fu W-M, Chen C–C, Su M-J, Liou H–H (2008) Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus. Epilepsia 49(5):888–897PubMedCrossRefGoogle Scholar
  20. 20.
    Doi T, Ueda Y, Nagatomo K, Willmore LJ (2009) Role of glutamate and GABA transportersin development of pentylenetetrazol-kindling. Neurochem Res 34:1324–1331PubMedCrossRefGoogle Scholar
  21. 21.
    Hussenet F, Boyet S, Nehlig A (1995) Long-term metabolic effects of pentylenetetrazol -induced status epilepticus in the immature rat. Neuroscience 67(2):455–461PubMedCrossRefGoogle Scholar
  22. 22.
    Li Z-P, Zhang X-Y, Lu X, Zhong M-K, Ji Y-H (2004) Dynamic release of amino acid transmitters induced by valproate in PTZ-kindled epileptic rat hippocampus. Neurochem Int 44:263–270PubMedCrossRefGoogle Scholar
  23. 23.
    Sherwin A, Robitaille Y, Quesney F, Olivier A, Leblanc R, Feindel W, Andermann E, Gotman J, Andermann F (1988) Exicitatory amino acids are elevated in human epileptic cerebral cortex. Neurology 38:920–923PubMedCrossRefGoogle Scholar
  24. 24.
    Janhua NA, Itano T, Kugoh T, Hosokawa K, Nakano M, Matsui H, Hatase O (1992) Familial increase in plasma glutamic aid in epilepsy. Epilepsy Res 11:37–44CrossRefGoogle Scholar
  25. 25.
    Wilson CL, Maidment NT, Ohomer MH, Behnke EJ, Ackerson L, Fried I, Engel J Jr (1996) Comparison of seizure related amino acid release in human epileptic hippocampus versus a chronic, kainite rat model of hippocampal epilepsy. Epilepsy Res 265:245–254CrossRefGoogle Scholar
  26. 26.
    Schroder H, Becker A (1996) The role of glutamate receptors in pentylenetetrazole kindling of rats-a neurochemical study. Neuropharmacology 35:A28CrossRefGoogle Scholar
  27. 27.
    Schroder H, Becker A, Loβner B (1993) Glutamate binding to brain membrane is increased in pentylenetetrazole-kindled rats. J Neurochem 60:1007–1011PubMedCrossRefGoogle Scholar
  28. 28.
    Schroder H, Becher A, Schroder V, Hollt V (1999) 3H-L-glutamate binding and K+-stimulated 3H-D-aspartate release from hippocampal tissue during the development of pentylenetetrazol kindling in rats. Pharmacol Biochem Behav 62:349–352CrossRefGoogle Scholar
  29. 29.
    Ekonomou A, Angelatou F (1999) Upregulation of NMDA receptors in hippocampus and cortex in the pentylenetetrazol-induced “kindling” model of epilepsy. Neurochem Res 24:1515–1522PubMedCrossRefGoogle Scholar
  30. 30.
    Hamberger A, Nystrom B, Larsson S, Silfvenius H, Nordborg C (1991) Amino acids in the neuronal microenvironment of focal human epileptic lesions. Epilepsy Res 9:32–43PubMedCrossRefGoogle Scholar
  31. 31.
    Carlson H, Ronne-Engstrom E, Ungerstedt U, Hillered L (1992) Seizure related elevations of extracellular amino acids in human focal epilepsy. Neurosci Lett 140:30–32PubMedCrossRefGoogle Scholar
  32. 32.
    During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:1607–1610APubMedCrossRefGoogle Scholar
  33. 33.
    Giorgi O, Orlandi M, Lecca D, Corda MG (1991) MK-801 prevents chemical kindling induced by pentylenetetrazol in rats. Eur J Pharmacol 193:363–635PubMedCrossRefGoogle Scholar
  34. 34.
    Sayin U, Cengiz S, Altug T (1993) Vigabatrin as an anticonvulsant against pentylenetetrazole seizures. Pharmacol Res 28:325–331PubMedCrossRefGoogle Scholar
  35. 35.
    da Silva LF, Pereira P, Elisabetsky E (1998) A neuropharmacological analysis of PTZ-induced kindling in mice. Gen Pharmac 31:47–50CrossRefGoogle Scholar
  36. 36.
    Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105PubMedCrossRefGoogle Scholar
  37. 37.
    Chapman AG (2000) Glutamate and epilepsy. J Nutr 130:1043S–1045SGoogle Scholar
  38. 38.
    Chao X-D, Fei F, Fei Z (2010) The role of excitatory amino acid transporters in cerebral ischemia. Neurochem Res 35:1224–1230PubMedCrossRefGoogle Scholar
  39. 39.
    White HS, Wolf HH, Woodhead JH, Kupferberg HJ (1998) The National Institutes of Health Anticonvulsant Drug Development Program: screening for efficacy. In: French J, Leppik I, Dichter MA (Eds.), Antiepileptic Drug Development. Advancesin Neurology vol. 76. Lip-pincott-Raven, Philadelphia, pp. 29–39Google Scholar
  40. 40.
    Lees G, Leach MJ (1993) Studies on the mechanism of action of the novel anticonvulsant lamotrigine (Lamactil) using primary neurological cultures from rat cortex. Brain Res 612:190–199PubMedCrossRefGoogle Scholar
  41. 41.
    Wang SJ, Sibra TS, Gean PW (2001) Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity. Neuro Report 12:2255–2258Google Scholar
  42. 42.
    Das A, McDowell M, O’Dell MC, Busch ME, Smith JA, Ray SK, Banik NL (2010) Post-treatment with voltage-gated Na+ channel blocker attenuates kainic acid-induced apoptosis in rat primary hippocampal neurons. Neurochem Res 35:2175–2183PubMedCrossRefGoogle Scholar
  43. 43.
    Waldmeier PC, Baumann PA, Wick P, Feldtrauer JJ, Stierlin C, Scmutz M (1995) Similar potency of carbamazepine, oxcarbazepine and lamotrigine in inhibiting the release of glutamate and other neurotransmitters. Neurology 45:1907–1913PubMedCrossRefGoogle Scholar
  44. 44.
    Afanas’ev I, Kudrin V, Rayevsky KS, Varga V, Saransaari P, Oja SS (1999) Lamotrigine and carbamazepine affect differentially the release of D-[3H]aspartate from mouse cerebral cortical slices. Neurochem Res 24:1153–1159PubMedCrossRefGoogle Scholar
  45. 45.
    Zachar G, Wagner Z, Tabi T, Balint E, Szoko E, Csillag A (2012) Differential changes of extracellular aspartate and glutamate in the striatum of domestic chicken evoked by high potassium or distress: an in vivo microdialysis study. Neurochem Res 37:1730–1737PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Yan Deng
    • 1
    • 2
  • Minghuan Wang
    • 3
  • Wei Wang
    • 1
  • Chao Ma
    • 2
  • Nongyue He
    • 1
    • 2
  1. 1.Hunan Key Laboratory of Green Packaging and Application of Biological NanotechnologyHunan University of TechnologyZhuzhouChina
  2. 2.State Key Laboratory of BioelectronicsSoutheast UniversityNanjingChina
  3. 3.School of Clinical MedicineSoutheast UniversityNanjingChina

Personalised recommendations